Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib.
Date
2022-08-16ICR Author
Author
Zhu, Z
Turner, NC
Loi, S
André, F
Martin, M
Diéras, V
Gelmon, KA
Harbeck, N
Zhang, C
Cao, JQ
Yan, Z
Lu, DR
Wei, P
VanArsdale, TL
Rejto, PA
Huang, X
Rugo, HS
Loibl, S
Cristofanilli, M
Finn, RS
Liu, Y
Type
Journal Article
Metadata
Show full item recordAbstract
While cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, combined with endocrine therapy (ET), are becoming the standard-of-care for hormone receptor-positive/human epidermal growth factor receptor 2‒negative metastatic breast cancer, further mechanistic insights are needed to maximize benefit from the treatment regimen. Herein, we conducted a systematic comparative analysis of gene expression/progression-free survival relationship from two phase 3 trials (PALOMA-2 [first-line] and PALOMA-3 [≥second-line]). In the ET-only arm, there was no inter-therapy line correlation. However, adding palbociclib resulted in concordant biomarkers independent of initial ET responsiveness, with shared sensitivity genes enriched in estrogen response and resistance genes over-represented by mTORC1 signaling and G2/M checkpoint. Biomarker patterns from the combination arm resembled patterns observed in ET in advanced treatment-naive patients, especially patients likely to be endocrine-responsive. Our findings suggest palbociclib may recondition endocrine-resistant tumors to ET, and may guide optimal therapeutic sequencing by partnering CDK4/6 inhibitors with different ETs. Pfizer (NCT01740427; NCT01942135).
Collections
Subject
Science & Technology
Life Sciences & Biomedicine
Oncology
ESTROGEN-RECEPTOR
BREAST-CANCER
TUMOR MICROENVIRONMENT
ENDOCRINE RESISTANCE
THERAPY
MECHANISMS
DISCOVERY
Research team
Molecular Oncology
Language
eng
Date accepted
2022-06-20
License start date
2022-08-16
Citation
npj Precision Oncology, 2022, 6 (1), pp. 56 -
Publisher
NATURE PORTFOLIO